Identification of a transcription factor like protein at the TOR locus in Leishmania mexicana amazonensis.
The TOR gene (TOxic nucleoside Resistance gene) was mapped to a 2.3 kb fragment on the amplified DNA from tubercidin resistant Leishmania (TUB). This DNA fragment conferred upon wild type cells resistance to tubercidin, inosine dialdehyde, formycin A and B and allopurinol riboside and a reduced ability to accumulate purine nucleobases and nucleosides. These properties were characteristic of the parental TUB cells which carried the intact amplified DNA and have been hypothesized to be caused by a reduction in the activity of the multiple purine transporters within this organism. The TOR gene was found to be partially homologous to the rodent and human Oct-6/SCIP/Tst-1 gene. It lacked, however, the POU specific domain of this class of transcription factors and contained only the first two helices of the POU homeodomain. This truncated homeodomain was not required to confer resistance upon wild type cells to toxic nucleosides, suggesting that TOR was not a repressor with independent DNA binding capability.
Detke
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University of North Dakota School of Medicine, Department of Biochemistry and Molecular Biology, Grand Forks 58202, USA. sdetke@mail.med.und.nodak.edu
D000493:Allopurinol / Q000031:analogs & derivatives / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology; D001692:Biological Transport; D003001:Cloning, Molecular; D004351:Drug Resistance; D005573:Formycins / Q000494:pharmacology; D017125:Genes, Protozoan / Q000235:genetics; D006801:Humans; D007288:Inosine / Q000031:analogs & derivatives / Q000494:pharmacology; D007894:Leishmania mexicana / Q000737:chemistry / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D050816:Octamer Transcription Factor-6; D010455:Peptides / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011687:Purines / Q000378:metabolism; D015183:Restriction Mapping; D012263:Ribonucleosides / Q000494:pharmacology; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014170:Transformation, Genetic; D014372:Tubercidin / Q000494:pharmacology
D000981:Antiprotozoal Agents; D005573:Formycins; C110928:NupM1 protein, Leishmania mexicana; C494178:POU3F1 protein, human; D010455:Peptides; D011687:Purines; D012263:Ribonucleosides; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6; C007390:inosine dialdehyde; D007288:Inosine; D000493:Allopurinol; C034550:formycin; D014372:Tubercidin; C021958:allopurinol riboside